伊博格碱阻滞HERG通道电流

Ibogaine blocks HERG currents

目的应用全细胞膜片钳技术观察抗毒瘾药物伊博格碱对异源转染Human ether-a-go-go-related(HERG)基因编码通道电流的影响。方法在人胚肾293细胞上转染野生型HERG基因,采用全细胞膜片钳技术记录HERG电流,观察99.5%纯度和95%纯度不同浓度1、5、10、50μmol/L伊博格碱对HERG电流阻滞的作用以及99.5%纯度5μmol/L伊博格碱对通道动力学的影响。结果 99.5%纯度和95%纯度的伊博格碱阻滞HERG电流的半数最大抑制浓度(IC50)无显著差异(P>0.05),分别为(4.09±0.69)μmol/L和(3.53±0.16)μmol/L。99.5%纯度的伊博格碱5μmol/L可逆性抑制HERG电流,使HERG通道电流电压依赖性的半激活电压左移[(-3.1±2.0)m V vs(-15.2±2.1)m V,P<0.01],半失活电压左移[(-45±3)m V vs(-59±3)m V,P<0.01];在所有测试电压下加快HERG通道失活;在测试电压-40 m V时,延缓HERG通道从失活中恢复[(891±103)ms vs(1 831±334)ms,P<0.05]。结论伊博格碱阻滞HERG通道电流,主要作用在HERG通道的失活状态。

Objective To investigate the effects of anti-addition drug ibogaine on Human ether-a-go-go-related （HERG） currents. Methods HERG currents were expressed in HEK293 cell line by transient transfection. Whole cell patch clamp technique was used to record HERG currents. Results There was no difference between 99.5 % purity ibogaine and 95% purity ibogaine in the IC50 for HERG blockade [ （4.09±0.69） μmol/L vs （3.53±0.16） μmol/L]. 99.5% purity ibogaine blocked HERG current reversely and significantly shifted the voltage dependent activation curve and inactivation curve in a negative direction. 99.5% ibogaine accelerated channel inactivation at all test voltage and delay the time constants of recovery from inactivation at -40 InV. Conclusion Ibogaine blocks HERG currents by binding to the inactive state. [ Chinese Journal of Cardiac Pacing and Electrophysiology, 2015,29 （ 6 ） ：562-566 ]